There is much evidence to suggest a neurotransmitter or neuromodulator role for the endogenous opiate-like peptides, the enkephalins, in mammalian brain. As such, they may mediate the integration of sensory information having to do with pain and emotion. Data have indeed accumulated which implicate these substances in pain, drug addition, and mental illness. The objective of the proposed research is to understand the functional role(s) of these endogenous peptides and to determine how their funnction(s) may be altered by drugs which affect the central nervous system. Specifically, we propose to study the characteristics of the in vitro release of enkephalins from various anatomical regions of rat brain and to examine the effects of other putative neurotransmitters (and/or neuromodulators) as well as a variety of centrally acting drugs on this release. We will further seek to determine if there are alterations in release characteristics in morphine tolerant and dependent nimals. Efforts will also be directed toward determining levels of te opiate peptides in several anatomical regions of brain at various stages of postnatal development and to determine if these levels are altered as a result of exposure of the animal to drugs, either during fetal development or during early postnatal life.